RGTA® Ischemic Wound

Heparan sulfate glycosaminoglycan mimetic improves pressure ulcer healing in a rat model of cutaneous ischemia-reperfusion injury

Miao Tong, MD; Bastiaan Tuk; Ineke M. Hekking; Mieke M. Pleumeekers, MD; Mireille B. Boldewijn, MD; Steven E.R. Hovius, MD, PhD; Johan W. van Neck, PhD

ABSTRACT

Pressure ulcers are a major clinical problem, with a large burden on healthcare resources. This study evaluated the effects of the heparan sulfate glycosaminoglycan mimetic, OTR4120, on pressure ulceration and healing. Ischemia-reperfusion (I-R) was evoked to induce pressure ulcers by external clamping and then removal of a pair of magnet disks on rat dorsal skin for a single ischemic period of 16 hours. Immediately after magnet removal, rats received an intramuscular injection of OTR4120 weekly for up to 1 month. During the ischemic period, normal skin perfusion was reduced by at least 60% and at least 20–45% reperfused into the ischemic region after compression release. This model caused sustained skin incomplete necrosis for up to 14 days and led to grade 2–3 ulcers.

OTR4120 treatment decreased the area of skin incomplete necrosis and degree of ulceration. OTR4120 treatment also reduced inflammation and increased angiogenesis. In OTR4120-treated ulcers, the contents of vascular endothelial growth factor, platelet-derived growth factor, and transforming growth factor beta-1 were increased. Moreover, OTR4120 treatment promoted early expression of alpha-smooth muscle actin and increased collagen biosynthesis. Long-term restoration of wounded tissue biomechanical strength was significantly enhanced after OTR4120 treatment. Taken together, we conclude that OTR4120 treatment reduces pressure ulcer formation and potentiates the internal healing bioavailability.